BI-201335. Treatment of hepatitis C virus serine protease NS3on-structural protein 4A (NS4A) inhibitor

摘要

Chronic hepatitis C affects an estimated 170 million people worldwide and is the leading indication for liver transplantation in the U.S. Until recently, eradication of chronic hepatitis C depended on the combination of pegylated interferon (pegIFN) and ribavirin (RBV). This combination is effective in only 40-50% of patients infected with hepatitis C virus (HCV) genotype 1, and 30-40% of patients co-infected with HIV. It also carries a high burden of side effects, mostly flu-like illness, fatigue, depression and anemia. This low-efficacy/high-toxicity regimen has motivated the search for a more potent treatment with an improved side effect profile. In this context, various therapeutic agents targeting viral enzymes critical to HCV replication have been identified. BI-201335 is a potent and selective HCV serine protease NS3onstructural protein 4A (NS4A) inhibitor that recently entered phase III clinical trials. In phase II trials, cure rates above 80% were reported for previously untreated patients, with the majority being eligible for shorter treatment duration. Its high potency, once-daily dosing and good safety profile suggest it could be included in future interferon-free directacting antiviral combinations.